Bevacizumab alone or in combination with irinotecan improved response
rates, PFS and OS compared with that typically seen in patients with recurrent
glioblastoma, according to the results of a phase-2 study.
Researchers conducted a multicenter, open-label study of 167 patients
randomly assigned bevacizumab (Avastin, Genentech) 10 mg/kg alone (n=85) or in
combination with irinotecan 340 mg/m2 or 125 mg/m2 (n=82)
once every two weeks. Patients who received the 340 mg/m2 dose of
irinotecan (36.6%) also received enzyme-inducing antiepileptic drugs.
The data, originally
presented at the 2008 ASCO Annual Meeting, were published in
The Journal of Clinical Oncology this week.
In the bevacizumab alone group, six-month PFS was 42.6%, objective
response rate was 28.2%, and median OS was 9.2 months. In the group receiving
both bevacizumab and irinotecan, six-month PFS was 50.3%, objective response
rate was 37.8%, and median OS was 8.7 months.
These numbers exceeded those assumed for traditional treatments. The
researchers assumed a 15% rate for six-month PFS with salvage chemotherapy and
irinotecan alone (P<.0001). The objective response rate was assumed
to be 5% for salvage chemotherapy compared with the bevacizumab group, and 10%
for irinotecan alone compared with the bevacizumab and irinotecan group
(P<.0001). The researchers also noted a trend for patients receiving
corticosteroids at baseline to take stable or decreasing doses over time.
Grade-3 or higher adverse events occurred in 46.4% of patients receiving
bevacizumab alone and in 65.8% of patients receiving bevacizumab and
irinotecan. The most common events included hypertension (8.3%) and convulsion
(6%) in the bevacizumab alone group; and convulsion (13.9%), neutropenia (8.9%)
and fatigue (8.9%) with bevacizumab plus irinotecan.
Researchers reported intracranial hemorrhage in 2.4% of patients in the
bevacizumab alone group and in 3.8% of patients in the bevacizumab and
Friedman HS. J Clin Oncol.
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